塞利尼索+硼替佐米+地塞米松治療多發性骨髓瘤患者療效顯著
作者：
小柯機器人發布時間：2020/11/16 14:07:18
波蘭西裡西亞醫科大學Sebastian Grosicki團隊比較了每周一次塞利尼索+硼替佐米+地塞米松，與每周兩次硼替佐米+地塞米松治療多發性骨髓瘤患者的療效。2020年11月14日，該研究發表在《柳葉刀》雜誌上。
塞利尼索與地塞米松聯用治療經過大量預處理的多發性骨髓瘤患者有一定療效。在一項臨床1b/2期研究中，口服塞利尼索與硼替佐米（一種蛋白酶體抑制劑）和地塞米松的組合可誘導高應答率，而周圍神經病變（硼替佐米的主要劑量限制性毒性）的發生率低。
研究組在21個國家/地區的123個研究機構進行了一項臨床3期的隨機開放標籤試驗。2017年6月6日至2019年2月5日，研究組招募了402例18歲及以上、以前曾接受過一到三線治療（包括蛋白酶體抑制劑）、多發性骨髓瘤的患者，將其隨機分組，其中195例接受每周一次塞利尼索+硼替佐米+地塞米松治療（三聯組），207例接受每周兩次硼替佐米+地塞米松治療（二聯組）。主要終點為無進展生存期。截至2020年2月20日，仍有55名患者接受隨機治療。
三聯組的中位隨訪時間為13.2個月，二聯組為16.5個月。三聯組的中位無進展生存期為13.93個月，顯著長於二聯組（9.46個月）。最常見的3-4級不良事件是血小板減少症（三聯組發生率為39％，二聯組為17%）、疲勞（13%與1%）、貧血（16％與10％）和肺炎（11%與11％）。二聯組患者周圍神經病變的發生率為34%，顯著高於三聯組（21%）。三聯組中有47名患者（24%）死亡，二聯組有62名（30%）。
研究結果表明，對於已經接受過一到三線治療的多發性骨髓瘤患者，每周一次進行塞利尼索+硼替佐米+地塞米松治療可顯著延長無進展生存期。
附：英文原文
Title: Once-per-week selinexor, bortezomib, and dexamethasone versus twice-per-week bortezomib and dexamethasone in patients with multiple myeloma (BOSTON): a randomised, open-label, phase 3 trial
Author: Sebastian Grosicki, Maryana Simonova, Ivan Spicka, Ludek Pour, Iryrna Kriachok, Maria Gavriatopoulou, Halyna Pylypenko, Holger W Auner, Xavier Leleu, Vadim Doronin, Ganna Usenko, Nizar J Bahlis, Roman Hajek, Reuben Benjamin, Tuphan K Dolai, Dinesh K Sinha, Christopher P Venner, Mamta Garg, Mercedes Gironella, Artur Jurczyszyn, Pawel Robak, Monica Galli, Craig Wallington-Beddoe, Atanas Radinoff, Galina Salogub, Don A Stevens, Supratik Basu, Anna M Liberati, Hang Quach, Vesselina S Goranova-Marinova, Jelena Bila, Eirini Katodritou, Hanna Oliynyk, Sybiryna Korenkova, Jeevan Kumar, Sundar Jagannath, Phillipe Moreau, Moshe Levy, Darrell White, Moshe E Gatt, Thierry Facon, Maria V Mateos, Michele Cavo, Donna Reece, Larry D Anderson, Jean-Richard Saint-Martin, Jacqueline Jeha, Anita A Joshi, Yi Chai, Lingling Li, Vishnuvardhan Peddagali, Melina Arazy, Jatin Shah, Sharon Shacham, Michael G Kauffman, Meletios A Dimopoulos, Paul G Richardson, Sosana Delimpasi
Issue&Volume: 2020/11/14
Abstract:
Background
Selinexor combined with dexamethasone has shown activity in patients with heavily pre-treated multiple myeloma. In a phase 1b/2 study, the combination of oral selinexor with bortezomib (a proteasome inhibitor) and dexamethasone induced high response rates with low rates of peripheral neuropathy, the main dose-limiting toxicity of bortezomib. We aimed to evaluate the clinical benefit of weekly selinexor, bortezomib, and dexamethasone versus standard bortezomib and dexamethasone in patients with previously treated multiple myeloma.
Methods
This phase 3, randomised, open-label trial was done at 123 sites in 21 countries. Patients aged 18 years or older, who had multiple myeloma, and who had previously been treated with one to three lines of therapy, including proteasome inhibitors, were randomly allocated (1:1) to receive selinexor (100 mg once per week), bortezomib (1·3 mg/m 2 once per week), and dexamethasone (20 mg twice per week), or bortezomib (1·3 mg/m 2 twice per week for the first 24 weeks and once per week thereafter) and dexamethasone (20 mg four times per week for the first 24 weeks and twice per week thereafter). Randomisation was done using interactive response technology and stratified by previous proteasome inhibitor therapy, lines of treatment, and multiple myeloma stage. The primary endpoint was progression-free survival in the intention-to-treat population. Patients who received at least one dose of study treatment were included in the safety population. This trial is registered at ClinicalTrials.gov, NCT03110562. The trial is ongoing, with 55 patients remaining on randomised therapy as of Feb 20, 2020.
Findings
Of 457 patients screened for eligibility, 402 were randomly allocated—195 (49%) to the selinexor, bortezomib, and dexamethasone group and 207 (51%) to the bortezomib and dexamethasone group—and the first dose of study medication was given between June 6, 2017, and Feb 5, 2019. Median follow-up durations were 13·2 months [IQR 6·2–19·8] for the selinexor, bortezomib, and dexamethasone group and 16·5 months [9·4–19·8] for the bortezomib and dexamethasone group. Median progression-free survival was 13·93 months (95% CI 11·73–not evaluable) with selinexor, bortezomib, and dexamethasone and 9·46 months (8·11–10·78) with bortezomib and dexamethasone (hazard ratio 0·70 [95% CI 0·53–0·93], p=0·0075). The most frequent grade 3–4 adverse events were thrombocytopenia (77 [39%] of 195 patients in the selinexor, bortezomib, and dexamethasone group vs 35 [17%] of 204 in the bortezomib and dexamethasone group), fatigue (26 [13%] vs two [1%]), anaemia (31 [16%] vs 20 [10%]), and pneumonia (22 [11%] vs 22 [11%]). Peripheral neuropathy of grade 2 or above was less frequent with selinexor, bortezomib, and dexamethasone (41 [21%] patients) than with bortezomib and dexamethasone (70 [34%] patients; odds ratio 0·50 [95% CI 0·32–0·79], p=0·0013). 47 (24%) patients in the selinexor, bortezomib, and dexamethasone group and 62 (30%) in the bortezomib and dexamethasone group died.
Interpretation
A once-per-week regimen of selinexor, bortezomib, and dexamethasone is a novel, effective, and convenient treatment option for patients with multiple myeloma who have received one to three previous lines of therapy.
DOI: 10.1016/S0140-6736(20)32292-3
Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32292-3/fulltext